LIPA geeni (10q23.31),LAL, Lipase A, lysosomaali happotyyppinen, Kolesteroliesterihydrolaasi (CESD)

https://www.ncbi.nlm.nih.gov/gene/3988

Also known as

LAL; CESD

Summary

This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase). This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides. Mutations in this gene can result in Wolman disease and cholesteryl ester storage disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

Expression

Broad expression in spleen (RPKM 177.6), small intestine (RPKM 113.4) and 21 other tissues See more

Related articles in PubMed

1. CRISPR/Cas9-Mediated Gene Editing in Human iPSC-Derived Macrophage Reveals Lysosomal Acid Lipase Function in Human Macrophages-Brief Report. Zhang H, et al. Arterioscler Thromb Vasc Biol, 2017 Nov. PMID 28882870,
2. Molecular and clinical characterization of a series of patients with childhood-onset lysosomal acid lipase deficiency. Retrospective investigations, follow-up and detection of two novel LIPA pathogenic variants. Pisciotta L, et al. Atherosclerosis, 2017 Oct. PMID 28881270
3. A Relative Deficiency of Lysosomal Acid Lypase Activity Characterizes Non-Alcoholic Fatty Liver Disease. Tovoli F, et al. Int J Mol Sci, 2017 May 25. PMID 28587063,  Free PMC Articl Abstract Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.KEYWORDS: liver cirrhosis; lysosomal acid lipase; non-alcoholic fatty liver disease; steatohepatitis; steatosis
   
   4. Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study. Angelico F, et al. Atherosclerosis, 2017 Jul. PMID 28396038 Abstract BACKGROUND AND AIMS:
   
   Blood lysosomal acid lipase (LAL) is reduced in non-alcoholic steatohepatitis, which is the major cause of cryptogenic cirrhosis (CC); few data on LAL activity in CC do exist. We investigated LAL activity in a cohort of patients with liver cirrhosis.METHODS:
   This is a multicentre cohort study including 274 patients with liver cirrhosis of different aetiology from 19 centres of Internal Medicine, Gastroenterology and Hepatology distributed throughout Italy. Blood LAL activity (nmol/spot/h) was measured with dried blood spot extracts using Lalistat 2.RESULTS:Overall, 133 patients had CC, and 141 patients had cirrhosis by other causes (61 viral, 53 alcoholic, 20 alcoholic + viral, 7 autoimmune). Mean age was 64.2 ± 13.4 years, and 28.5% were women. Patients with CC were older compared to other aetiology-cirrhosis, with a lower Child-Turcotte-Pugh (CTP, p=0.003) and MELD (p=0.009) score, and a higher prevalence of cardio-metabolic risk factors and previous ischemic events. In the whole cohort, median LAL activity value was 0.58 nmol/spot/h, 0.49 and 0.65 in the groups of CC and known-aetiology cirrhosis, respectively (p=0.002). The difference remained significant after adjustment for white blood cells count (p=0.001). Multivariable linear regression analysis showed that CC (vs. known aetiology, Beta = -0.144, p=0.018), platelet count (Beta = 0.398, p < 0.001) and CTP score (Beta = -0.133, p=0.022) were associated with log-LAL activity. Similar results were found using MELD as covariate.CONCLUSIONS:
   

   We found a marked reduction of LAL activity in patients with cryptogenic cirrhosis compared to the other known aetiologies. A prospective study will clarify the role of LAL in chronic liver diseases.Copyright © 2017 Elsevier B.V. All rights reserved.

   
   
   5. Coronary Artery Disease-Associated LIPA Coding Variant rs1051338 Reduces Lysosomal Acid Lipase Levels and Activity in Lysosomes. Morris GE, et al. Arterioscler Thromb Vasc Biol, 2017 Jun. PMID 28279971, Free PMC Article... conclusion, our findings suggest that the CAD-associated variant rs1051338, which causes a missense change in the signal peptide of LAL, disrupts the normal sorting and transport of LAL to the lysosome. LAL containing the risk allele is prone to cytosolic proteasomal degradation, reducing lysosomal LAL protein and activity. Understanding how this affects cholesterol metabolism may provide novel therapeutics for CAD through the modulation of macrophage cholesterol concentration

See all (66) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene